This review explores the intricate relationship between gut microbiota (GM) and tuberculosis (TB). The figure illustrates the bidirectional effects between GM dynamics and TB progression, as well as the interactions between the GM and antituberculosis drugs. It also explores the role of GM in the immune response to TB and its potential as a target for the diagnosis and treatment of TB. Finally, the application of multi-omics and artificial intelligence (AI) technologies in GM-TB research is highlighted. The review aims to shed light on the complex interplay between GM and TB, paving the way for innovative strategies in TB management.
Inoculation with plant growth-promoting rhizobacteria SQR9 enhances cooperative behaviors and compatibility within the microbial community, promoting plant growth. Building on these interactions, synthetic Bacillus consortia were designed based on phylogenetic relationships and social cooperation, where moderately related consortia exhibited stronger plant growth-promoting effects. This design strategy underscores the importance of microbial social dynamics in optimizing synthetic communities for sustainable agriculture.
Multi-omics sequencing and correlation analysis identified the beneficial role of Faecalibacterium prausnitzii (F. prausnitzii)-derived butyric acid (BA) as a key metabolite in the restoration of valve function in calcific aortic valve disease (CAVD). The therapeutic efficacy of BA in attenuating CAVD progression was confirmed in vitro, ex vivo, and in vivo. Subsequent mechanistic investigations revealed that BA reshape glycolysis through site-specific inhibition of lactylation at the Lys-263 residue of GAPDH, which is mediated by competitive inhibition of butyrylation at the same site.
Prenatal exposure to glucocorticoids is linked to long-term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats result in sex-specific long bone dysplasia in offspring, including reduced peak bone mass (PBM) and heightened osteoporosis risk in female offspring. Multi-omics profiling and fecal microbiota transplantation show that PPE alters maternal gut microbiota composition and depletes the microbial metabolite daidzein (DAI). DAI deficiency suppresses Hoxd12 expression, impairs osteogenesis, and leads to PBM decline in female offspring. In bone marrow-derived mesenchymal stem cells from PPE female offspring, DAI promoted Hoxd12 expression and osteogenic differentiation. Notably, DAI supplementation restored H3K9ac levels, enhanced Hoxd12 expression, and promoted osteogenic differentiation through the ERβ/KAT6A pathway. Furthermore, maternal DAI supplementation during pregnancy prevented osteoporosis susceptibility in PPE female offspring and alleviated functional abnormalities in multiple organs, including the liver, hippocampus, ovary, and adrenal gland. In conclusion, PPE induces multiorgan dysplasia and increases disease predisposition (e.g., osteoporosis) in female offspring by disrupting maternal gut microbiota and depleting DAI. Maternal DAI supplementation provides a promising preventive strategy to counteract these adverse outcomes.
In this study, we found evidence of phage-mediated horizontal transfer of virulence genes in Salmonella enterica in global habitats from a molecular evolutionary perspective. Notably, csrA, a global regulator in Salmonella enterica, curbed horizontal gene transfer by inhibiting the cyclization and release of prophage. This is a novel finding in phage–bacteria interactions that provides new ideas for controlling pathogenic bacteria in the environment.
This study investigates the vertical transmission of maternal microbiota in chickens and how it is modulated by maternal soyasaponin supplementation. Using a model spanning the reproductive tract, egg components, and developing chicks, we show that maternal gut and reproductive microbiota, including Bifidobacterium adolescentis (B. adolescentis), are transmitted via the yolk sac. Soyasaponin enhances this transmission and promotes B. adolescentis-derived Gamma-aminobutyric acid (GABA) production. GABA modulates chick intestinal development by suppressing autophagy and apoptosis pathways and activating proliferation and differentiation. These effects are mediated through GABA receptors. The study highlights the interplay between host genetics, maternal diet, and microbiota inheritance, offering insights into nutritional strategies to optimize offspring intestinal health.
Cold atmospheric plasma (CAP) represents an emerging onco-therapeutics that can specifically ablate cancer cells without harming their healthy peers via redox perturbation. CAP medicine in breast cancer (CAPmed-BC) is the first reservoir of multi-level omics data including whole transcriptome, acetylome, lactylome, proteome, phosphorylome that records the responses of different types of breast cancer cells to CAP treatment. Being the first functional module of Hiplo, CAPmed-BC can be used to capture the dynamics, functionality, and metabolism of triple negative breast cancer cells in response to CAP treatment, and is unique in interrogating cell metabolic alterations through coupled analysis of acetylome and lactylome.
In this study, 19 overweight participants, with or without type 2 diabetes mellitus, underwent 14 days of normal-diet observation followed by 14 days of dietary fiber intervention. Fecal samples and continuous glucose monitoring data were collected daily throughout the 28-day period. Using guild-based analysis of individual-level networks and time-series approaches, we captured the dynamic responses of gut microbiota, revealing multiple abundance-shift patterns that are often overlooked by conventional sampling strategies. By integrating multi-omics data with time-delayed analysis, we further identified key microbial members and metabolites associated with host metabolic improvements, thereby providing reliable targets for subsequent mechanistic investigations.
This study revealed spatio-temporal characteristics of gastrointestinal resistome in a cow-to-calf model and the pattern of their spread to the environment and offspring in the dairy production system. The gastrointestinal tract of dairy cows is a natural reservoir of resistomes and distinguished by gut sites and regions. The resistance profiles of different ecological niches (meconium, colostrum, soil, and water) were unique, and most of the features were shared with the maternal source. In the early life, antibiotics resistance genes may acquire from the maternal source, and diet and age are the primary regulatory factors of the resistome. Mobile genetic elements are an important medium between various ecological niches interactions which may occur most frequently from the soil and waste water.
A single-cell atlas was established to reveal the molecular characteristics of early gastric cancer (EGC). In combination with organoids, animal models, and clinical samples, it was found that subpopulations such as pit mucous-like cell (PMC-like), proliferating cell (PC), CH25H+ CD4+ T cell, IL-33+ endothelial cell, and ADAMTSL2+ endothelial cell are specifically abundant in EGC. Mechanistically, IL-33 expressed by endothelial cells can upregulate the adhesion molecules PECAM1 and CD34 to facilitate angiogenesis. Meanwhile, IL-33+ endothelial cells can up-regulate the expression of KRT17 in EGC organoids to promote tumor growth.
RepliChrom is an interpretable machine learning model that predicts enhancer-promoter interactions using DNA replication timing across multiple cell types. By integrating replication timing with chromatin interaction data from multiple experimental platforms, it accurately distinguishes true interactions and reveals promoter-region signals as key regulatory drivers. Importantly, the RepliChrom uncovers cancer-specific chromatin patterns in leukemia, offering mechanistic insights into how replication timing shapes long-range gene regulation in both normal and diseased genomes.
METTL5 catalyzes the N6-methyladenosine (m6A) methylation at A1771 in 18S rRNA, a modification essential for its association with the ribosomal protein RPL24A, facilitating the assembly of 80S ribosome. This facilitates the translation of mRNAs encoding the detoxifying glutathione S-transferase (GST) enzymes, thereby maintaining normal reactive oxygen species (ROS) levels and ensuring proper abscisic acid (ABA) responses. In mettl5 mutants, the absence of m6A1771 compromises RPL24A incorporation and ribosome assembly, impairing the translation of GSTs. This results in ROS excessive accumulation and hypersensitivity to ABA.
Multi-omics approaches revealed how nanoplastics with different surface charges influence antibiotic resistance in Escherichia coli K12. Positively charged nanoplastics enhanced antibiotic resistance by upregulating genes and proteins linked to oxidative stress tolerance and efflux pumps, and promoted antibiotic resistance genes transfer via conjugation and transformation. In contrast, negatively charged nanoplastics disrupted biofilm formation and metabolism, potentially reducing antibiotic resistance. These findings highlight the critical role of nanoplastics' surface properties in shaping microbial resistance dynamics and highlight emerging risks posed by nanoplastics to public health through accelerated antibiotic resistance propagation.
In this study, we reveal that macrophage-derived reactive oxygen species (ROS) can trigger the rapid formation of Salmonella aggresomes, which substantially contribute to the increased frequency of persisters induced by phagocytosis. Salmonella containing aggresomes exhibited a dormant phenotype characterized by reduced adenosine triphosphate (ATP) levels and decreased metabolic activity. Furthermore, these dormant bacteria showed upregulated expression of Salmonella pathogenicity island 1 (SPI-1)-encoded type III secretion system (T3SS)-related genes, followed by later expression of SPI-2 T3SS-related genes when macrophages ROS production declined. Our results demonstrate that Salmonella containing aggresomes can enter a dormant state to escape antibiotic attack, while crucially maintaining the ability to resuscitate when the stress environment is improved. Research on bacterial aggresomes could potentially provide therapeutic strategies to combat bacterial antibiotic persistence.
scRiskCell is an interpretable intelligent computational framework that leverages nearly 500,000 islet cell expression profiles from 106 donors across different continuous disease states. By calculating the intrinsic relationship between donor disease states and cell expression profiles, it assigns a pseudo-cell state index to each cell. Sorting the pseudo-indexes of cells enables the identification of risk cells truly disrupted by the disease. Importantly, scRiskCell reveals the dynamic aggregation pattern of risk cells during disease progression, providing mechanistic insights for early disease prediction and clinical dynamic monitoring of disease progression.
Randomized double-blind trials have shown that probiotic mixtures significantly increase high-density lipoprotein (HDL) levels and reduce the risk of cardiovascular disease mortality in end-stage renal disease (ESRD) patients. Meta-analysis with prospective cohort studies further confirms that elevated HDL is a protective factor for ESRD outcomes. In severe renal injury models, including 5/6 nephrectomy and apolipoprotein E-deficient (ApoE−/−) mice, probiotics restored cardiac function, mirroring the cardioprotective effects seen in humans. Mechanistic studies indicate that probiotics enhance intestinal HDL3 production through the insulin-mediated SP1(P)-CYP27A-LXRα/β-ABCA1 pathway, thereby maintaining HDL metabolic homeostasis. This study reveals a novel link between probiotic intervention and host cholesterol metabolism, offering a previously unexplored strategy for reducing cardiovascular risk in ESRD patients.
The study included 163 patients with muscle-invasive bladder cancer (MIBC) from 14 hospitals, categorized into the neoadjuvant immunotherapy-combined-modality therapy (Neoimmu-CMT), trimodal therapy (TMT), and neoadjuvant chemotherapy-combined-modality therapy (NAC-CMT) subgroups. Propensity score matching (PSM) was utilized to mitigate baseline variability. Univariate and multivariate Cox analyses were used to identify potential prognostic factors. Biomarker assessment comprised immunohistochemistry and single-cell RNA sequencing. After PSM, Neoimmu-CMT demonstrated superior efficacy over NAC-CMT and comparability to TMT. A clinical complete response to neoadjuvant treatment and lower clinical T stage were positive prognostic factors for Neoimmu-CMT. Biomarker analysis showed that the immune phenotype of the tumor microenvironment (TME) was closely associated with bladder preservation outcomes. We assessed the potential relationship between various cell types in the TME and bladder preservation outcomes using single-cell RNA sequencing. The results showed that the dynamic distribution of fibroblast and NK/T cell subclusters was associated with bladder preservation outcomes. In the future, the development of Neoimmu-CMT will substantially expand its application in bladder preservation therapies.
We developed PMAT2, an advanced toolkit for lineage-specific de novo assembly of plant, animal, and fungal mitochondrial genomes, as well as plant chloroplast genome. PMAT2 leverages optimized graph-based strategies tailored to organelle genome complexity, enabling complete and accurate assemblies, even with approximately 1 × highly accurate PacBio high-fidelity (HiFi) reads. By assembling 150 organellar genomes across diverse lineages, PMAT2 outperformed existing tools in assembly completeness. The source code for PMAT2 is publicly available at https://github.com/aiPGAB/PMAT2.
Using a robust functional metagenomics approach, we demonstrated that polar environments are important reservoirs of novel antibiotic resistance genes (ARGs). DNA was initially extracted from cultured bacterial consortia in the polar soils and recombined into plasmid vectors and then transformed into Escherichia coli (E. coli) for the subsequent screening of antibiotic resistance. Consequently, we identified 671 novel polar ARGs with experimentally verified resistance against multiple clinical antibiotics (cefotaxime, folate synthesis inhibitors, and clindamycin). Bioinformatics analysis revealed that novel polar ARGs had limited mobility and dissemination potential and were seldom carried by human bacterial pathogens. Overall, this study offers a comprehensive perspective on previously overlooked novel ARGs in polar regions, advancing our understanding of environmental resistomes.